Decoding the complexity of delayed wound healing following Enterococcus faecalis infection

Area of Science:

• Wound healing research
• Microbiology
• Immunology
• Transcriptomics

Background:

• Wound infections, common in diabetic foot ulcers and surgical sites, delay healing and increase morbidity.
• Enterococcus faecalis is frequently detected in non-healing wounds, yet its role in chronic wound pathogenesis is not well understood.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms by which Enterococcus faecalis infection impacts wound healing.
• To create a single-cell transcriptomic atlas of infected versus uninfected wounds.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on infected and uninfected mouse wound models.
• Analysis of over 23,000 cells to characterize the cellular and transcriptomic landscape.
• In vitro and in vivo experiments to assess macrophage polarization and cell interactions.

Main Results:

• Infected wounds exhibited distinct transcriptional and metabolic alterations compared to uninfected wounds.
• Keratinocytes and fibroblasts showed dysregulated transcriptomes, contributing to an anti-inflammatory environment.
• E. faecalis infection induced premature, incomplete epithelial-mesenchymal transition in keratinocytes and modulated M2-like macrophage polarization.
• Macrophage-neutrophil crosstalk was identified, regulating chemokine signaling and promoting anti-inflammatory interactions with endothelial cells.

Conclusions:

• E. faecalis infection significantly alters the wound microenvironment, promoting immunosuppression and hindering normal healing processes.
• The study provides novel insights into the molecular dialogue between bacteria, immune cells, and structural cells during chronic wound infections.
• Targeting E. faecalis-mediated immunosuppression may offer therapeutic strategies for improving chronic wound healing.